Design, Synthesis, and Biological Evaluation of Substituted Pyrimidines as Potential Phosphatidylinositol 3‑Kinase (PI3K) Inhibitors

Three series of substituted
pyrimidines were designed and synthesized. All target compounds were
screened for kinase inhibitory activities against PI3Kα, and
most IC50 values were found within the nanomolar range.
Compounds 5d and 5p displayed comparable
activities relative to the positive control 5a. 5p also showed a significant isozyme selectivity (PI3Kβ/α).
Furthermore, the cytotoxicities of these pyrimidines against human
cancer cell lines were evaluated and the in vivo anticancer effect
of 5d was also tested.

设计并合成了三系列取代嘧啶化合物。所有目标化合物均针对PI3Kα进行了激酶抑制活性的筛选，其中大多数IC50值位于纳摩尔范围内。化合物5d和5p与阳性对照5a相比，表现出可比的活性。5p还显示出显著的同工酶选择性（PI3Kβ/α）。此外，对这些嘧啶化合物对人癌细胞系细胞毒性的评估以及对5d体内抗癌效果的测试也已完成。